This is a renewal application for the MSTP at UT Southwestern which trains MD/PhD physician-scientists to bring the principles of experimental science to bear on fundamental problems in human disease and to translate that understanding into the next generation of effective patient care. The Program is entering its 25th year of continuous NIH funding. During the previous 5-year funding period, the UT Southwestern MSTP increased the number of applications by 2.5- to 3-fold by converting its application process to the national AMCAS system. Candidates offered admission to the Program present strong academic credentials (Avg. GPA = 3.77, Avg. MCAT = 35.6) and offers of admission are extended to ~10% of applicants. Between 10 and 16 students enrolled in the Program in each of the last five classes and there are currently 97 MSTP students. The average time to degree for the last five graduating classes was 8.3 years. Newly enacted curriculum modifications will reduce the average time to degree to less than 8 years. MSTP students typically complete 3 research rotations and 2 years of medical school before embarking on dissertation research. During the research years, students take graduate courses, pass a qualifying exam and work in the lab of one of the ~250 faculty members on the Graduate School faculty. MSTP mentors are well-funded (avg. $1.4M/PI) and typically oversee research in medically-relevant basic science projects. MSTP students select mentors for rotations/PhD research across the full spectrum of faculty and complete their PhD research with strong records of productivity, producing an average of 4 publications. Program graduates most often move on to clinical residencies (35/37 in last award term) at excellent institutions. The MSTP co-Directors are active physician-scientists with distinguished records in research and clinical medicine. The co-Directors establish Program policy and guide students through the MD/PhD path together with an Associate Dean, also an active scientist on UT Southwestern faculty, who manages program administration. Together with the co-Directors and Assoc. Dean, a 19 member Steering Committee operates as an admissions committee and helps set Program policies. In its 24 years, the MSTP has graduated 124 MSTP-funded students and career outcomes support the original NIH mandate for the Program: 89% of graduates who are in independent positions are doing medical research in academic medicine (86%) or pharmaceutical industry positions (3%).